: The overall objective of this grant is an in-depth investigation of pharyngoesophageal and laryngeal function in health and disease as it relates to gastroesophageal-pharyngeal reflux and aspiration. Gastroesophageal reflux disease is the most common malady of the esophagus. It is estimated that 7-10 percent of the US population suffers from various degrees of this disease. This translates into a significant burden on health care resources. However, complications of reflux disease induced outside the esophagus; namely in the aerodigestive and airway tracts, are now becoming increasingly recognized. For example, it is estimated that 410 percent of laryngeal diseases seen in ENT clinics are associated with reflux disease. However, progress in this field has lagged behind investigations in reflux related esophageal disorders. A substantial gap exists in our knowledge in regard to mechanisms of protection of supraesophageal regions from contact of gastric acid and pathophysiological basis of reflux related lesions in this region. Our specific objectives are: 1) to determine the pathophysiological basis of supraesophageal complications of gastroesophageal reflux disease. This section will include: characterization of regional pharyngeal distribution of gastric refluxate; characterization of the airway defensive reflexes against aspiration of gastroesophagopharyngeal reflux in the sleep state; determination of the effect of alcohol abuse on airway protective reflexes; and UES resistive function against esophagopharyngeal transit; physiology and pathophysiology of UES reflex response to gastroesophageal reflux, and 2) to investigate the sensory physiology of airway protective mechanisms. This section will include: characterization of the pharyngeal sensory field in relation to aerodigestive reflexes; functional localization of brain stem nuclei controlling esophageal and pharyngeal airway protective reflexes; and determination of the cerebral cortical representation of esophageal and pharyngeal viscerosensation as well as neuro-anatomical validation of FMRI cerebral response to esophageal stimulation. Individual, but interrelated protocols are proposed to achieve our objectives and will be executed by our multidisciplinary, interdepartmental team.